The sirtuin-associated human senescence program converges on the activation of PAPPA

被引：16

作者：

Bi, Shijia ^{[2
,4
]}

Jiang, Xiaoyu ^{[1
,2
,4
]}

Ji, Qianzhao ^{[1
,2
,4
]}

Wang, Zehua ^{[2
,4
]}

Ren, Jie ^{[3
,4
,5
,17
,18
]}

Wang, Si ^{[7
,8
,9
,19
]}

Yu, Yang ^{[10
]}

Wang, Ruoqi ^{[4
,16
]}

Liu, Zunpeng ^{[2
,4
]}

Liu, Junhang ^{[1
,2
,4
]}

Hu, Jianli ^{[3
,4
]}

Sun, Guoqiang ^{[1
,2
,4
]}

Wu, Zeming ^{[1
,2
,5
,6
]}

Diao, Zhiqing ^{[2
,4
]}

Li, Jingyi ^{[1
,2
,4
,5
,6
]}

Sun, Liang ^{[11
,12
,13
]}

Belmonte, Juan Carlos Izpisua ^{[15
]}

Zhang, Weiqi ^{[3
,4
,5
,14
]}

Liu, Guang-Hui ^{[1
,2
,4
,6
,7
,8
,9
,14
]}

Qu, Jing ^{[2
,4
,5
,6
]}

机构：

[1] Chinese Acad Sci, State Key Lab Stem Cell & Reprod Biol, Inst Zool, Beijing 100101, Peoples R China

[2] Chinese Acad Sci, State Key Lab Membrane Biol, Inst Zool, Beijing 100101, Peoples R China

[3] Chinese Acad Sci, Key Lab Organ Regenerat & Reconstruct, Beijing 100101, Peoples R China

[4] Chinese Acad Sci, Beijing Inst Genom, CAS Key Lab Genom & Precis Med, Beijing 100101, Peoples R China

[5] Univ Chinese Acad Sci, Beijing 100049, Peoples R China

[6] Chinese Acad Sci, Inst Stem Cell & Regenerat, Beijing 100101, Peoples R China

[7] Beijing Inst Stem Cell & Regenerat Med, Beijing 100101, Peoples R China

[8] Capital Med Univ, Adv Innovat Ctr Human Brain Protect, Beijing 100053, Peoples R China

[9] Capital Med Univ, Natl Clin Res Ctr Geriatr Disorders, Xuanwu Hosp, Beijing 100053, Peoples R China

[10] Capital Med Univ, Beijing Municipal Geriatr Med Res Ctr, Aging Translat Med Ctr, Int Ctr Aging & Canc,Xuanwu Hosp, Beijing 100053, Peoples R China

[11] Peking Univ Third Hosp, Ctr Reprod Med, Dept Obstet & Gynecol, Beijing 100191, Peoples R China

[12] Chinese Acad Med Sci, NHC Key Lab Geriatr Inst Geriatr Med, Natl Ctr Gerontol, NHC Beijing Inst Geriatr,Beijing Hosp, Beijing 100730, Peoples R China

[13] Kunming Med Univ, Affiliated Hosp 1, Dept Clin Lab, Kunming 650032, Peoples R China

[14] Aging Biomarker Consortium, Beijing 100101, Peoples R China

[15] Altos Labs, San Diego, CA 92121 USA

[16] Chinese Acad Sci, Inst Biophys, Natl Lab Biomacromol, Beijing 100101, Peoples R China

[17] Chinese Acad Sci, Beijing Inst Genom, Key Lab RNA Sci & Engn, Beijing 100101, Peoples R China

[18] China Natl Ctr Bioinformat, Beijing 100101, Peoples R China

[19] Fifth Peoples Hosp Chongqing, Chongqing 400062, Peoples R China

来源：

DEVELOPMENTAL CELL | 2024年 / 59卷 / 08期

关键词：

PLASMA-PROTEIN-A; TRANSCRIPTIONAL ACTIVATION; READ ALIGNMENT; STEM-CELLS; DOMAINS; ORGANIZATION; EXPRESSION; REGULATOR; STRESS; CTCF;

D O I：

10.1016/j.devcel.2024.02.008

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Sirtuins are pro-longevity genes with chromatin modulation potential, but how these properties are connected is not well understood. Here, we generated a panel of isogeneic human stem cell lines with SIRT1- SIRT7 knockouts and found that any sirtuin deficiency leads to accelerated cellular senescence. Through large-scale epigenomic analyses, we show how sirtuin deficiency alters genome organization and that genomic regions sensitive to sirtuin deficiency are preferentially enriched in active enhancers, thereby promoting interactions within topologically associated domains and the formation of de novo enhancer-promoter loops. In all sirtuin-deficient human stem cell lines, we found that chromatin contacts are rewired to promote aberrant activation of the placenta-specific gene PAPPA, which controls the pro-senescence effects associated with sirtuin deficiency and serves as a potential aging biomarker. Based on our survey of the 3D chromatin architecture, we established connections between sirtuins and potential target genes, thereby informing the development of strategies for aging interventions.

引用

页码：991 / 1009.e12

页数：32

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